Management of Osteomyelitis:

Emphasis on Methicillin-Resistant Staphylococcus aureus (MRSA)

Consensus Guidelines from SFGH Orthopedic Surgery, Infectious Diseases, and Infectious Diseases Pharmacy

 

I.        Consult Infectious Diseases when intravenous antibiotics are planned for osteomyelitis.  This is particularly important when MRSA is the responsible organism, as outcomes with therapy of this infection are being monitored prospectively.

II.       Define the goals of therapy.  Is therapy, preferably a combined medical/surgical approach, intended to be curative? Or, should suppressive or intermittent courses of treatment be used?  Oral antibiotics (or a shorter intravenous course followed by oral antibiotics) may be more appropriate when the intent is to suppress the infection either indefinitely or until a necessary surgical procedure (e.g. removal of hardware) can be performed.

III.      Duration of therapy should be determined in conjunction with plans for appropriate surgery/debridement per the Orthopedics service.

 

For confirmed MRSA bone infections known or presumed to be monomicrobial and intravenous therapy planned:

I.        Failure with 6 weeks of IV vancomycin alone is common – as high as 46% in a recent survey at SFGH.

II.       An initial treatment course followed by extended oral therapy is recommended whenever this is feasible.  In addition, oral rifampin should be used in combination with vancomycin.  

a.       Initial therapy should generally be 6 weeks in duration.

                              i.      First choice initial therapy is vancomycin IV  (30mg/kg/day divided in two or three doses) + rifampin 600 mg as a single daily dose or 300 mg BID.  Vancomycin should be adjusted so that trough levels are 10 – 20 (target ~ 15). 

                             ii.      In patients who cannot receive rifampin (e.g. isolate is rifampin resistant, patient has severe hepatic disease, or there are issues of drug interactions with rifampin) second choice therapy is clindamycin 600 mg IV q 8 hours.

                              iii.      In patients who cannot receive regimens i. or ii., third choice therapy is with linezolid 600mg PO BID.

                              iv.      If options i. – iii. are not possible, vancomycin monotherapy or other regimens can be considered.  

b.      Follow-on, “consolidation” therapy should be continued for approximately 2-3 months, assuming adequate clinical response.  MRSA must be susceptible to the listed antibiotics in order to select the regimen.

                             i.      First choice therapy is levofloxacin 500 mg PO daily (or ciprofloxacin 500mg PO BID for MediCal patients) + rifampin 300mg PO BID.  

                            ii.      Second choice therapy is clindamycin 300mg PO BID + rifampin 300mg PO BID.

                            iii.      Third choice therapy is TMP/SMX 2 DS tablets PO BID  + rifampin 300 mg PO BID.

                            iv.      Fourth choice therapy is doxycycline 100mg PO BID  + rifampin 300 mg PO BID.

                            v.      In patients who cannot receive rifampin the above antibiotics (with the exception of fluoroquinolones) can be used as monotherapy in the same order of preference. Fluoroquinolones are not recommended as monotherapy, since resistance may develop while on therapy. 

                            vi.      Extended linezolid therapy can be considered in some circumstances.  However, linezolid has several important toxicities associated with long term use and is much more expensive than the other oral alternatives. 

                            vii.      As further data become available, these recommendations may be revised.

 

Note: Dosing recommendations above are for patients with CLCr > 50 ml/min. For patients with renal insufficiency or who are on hemodialysis, consult with the ID pharmacist for dosing recommendations.

 

Chronic osteomyelitis with overlying ulcer (e.g. diabetic foot infection):

Many of these patients can be treated with oral antibiotics in conjunction with surgical debridement.  When the pathogen(s) is/are known, therapy should be pathogen directed.  For empirical therapy, a fluoroquinolone + clindamycin can be considered.  If MRSA is the primary pathogen, the consolidation regimens listed above can be used as initial therapy.  If medical therapy only is used, cure is achieved in a minority of cases; oral regimens are preferred, particularly after acute infection has been treated. 

 

Patients receiving methadone:

Induction of methadone metabolism is a concern when rifampin is being used.  When withdrawal symptoms occur, they can usually be managed by titrating the methadone dose up after several days of rifampin.  Please consult with ID pharmacy and/or the patient’s methadone maintenance program for recommendations.